ISS: Engineering Stem Cell-Derived Cardiac Microtissues with Metabolic Regulators in Space to Promote Cardiomyocyte Maturation

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Cardiac muscle cells generated from stem cells could be used to replace damaged cells in patients with heart disease, which is the leading cause of death in the United States. Scientists have also used these cells to study heart disease and drug responses. Currently, when scientists grow cardiac muscle cells in a dish, the characteristics of these cells look like the heart cells at the early developmental stage; their shape, size, and function resemble immature heart cells. Ideally, more mature cardiac muscle cells are needed in cardiac cell replacement therapy and the study of heart disease. Therefore, developing methods to accelerate the maturation of cardiac muscle cells is highly significant. The unique environment of the International Space Station (ISS) is known to provide beneficial effects on human cardiac precursors to help their growth and differentiation. In this project, the research team will investigate the maturation of stem cell-derived cardiac muscle cells by growing these cells in tissue-like structures in the ISS. The investigators also plan to develop a technology to promote cardiac muscle cell maturation in microtissues that are suitable for large-scale production, a requirement essential for translational research. This project also incorporates the training of young scientists and students and provides science-learning opportunities for kids in a local hospital in the Children's Healthcare of Atlanta system. The goal of this project is to establish a multipronged approach combining microgravity, tissue engineering and metabolic regulation to promote the maturation of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs). First, the investigators will optimize the design of tissue engineering and cell culture conditions in ground-based experiments by examining the effect of simulated microgravity, cell composition and metabolic regulation. Second, the hiPSC-CM microtissues will be cultured in the ISS. The experiments will be performed within a perfusion system that is suitable for suspension cell culture and has gas permeable membranes that allow sufficient gas exchange for cell growth. The cells will remain in the same culture units throughout the experiment and cell morphology will be monitored once a week utilizing an inverted phasecontrast microscope currently available at the ISS, and the imaging data will be transmitted for ground-based control and data retrieval. Following spaceflight, the researchers will investigate molecular and functional characteristics of the hiPSC-CMs. Exposure of hiPSC-CM microtissues to microgravity in space is expected to eliminate shear stress and consequently enhance cell-cell and cell-matrix interactions within multicellular architectures. Findings from this project will provide insights into the molecular regulation of accelerated hiPSC-CM maturation. Applying these insights to the research on earth could assist in the production of more mature hiPSC-CMs to enhance their potential application in regenerative medicine, the study of heart disease and drug development. (Project integration and operation on the ISS will be provided by the Center for the Advancement of Science in Space (CASIS) implementation partner, BioServe.)This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.